This project will examine cardiac, pulmonary and arterial baroreflex control of the circulation in an animal model of chronic heart failure (HF). Chronic tachycardia will be used to produce a state of congestive HF. This model results in cardiac dilation, reduced contractility, pulmonary edema and exercise intolerance. Specifically, we will determine: 1) the arterial baroreflex control of sympathetic nerve activity in conscious animals with HF and whether or not the baroreflex is primarily responsible for the chronic increase in sympathetic outflow in HF. Preliminary data suggests that plasma norepinephrine increases in this model of HF even if the arterial baroreceptors have been ablated. We will extend these experiments to the direct measurements of sympa- thetic outflow. If these data are confirmed it would mean that the accepted notion of poor baroreflex function causing a chronic increase in sympathetic outflow in HF is no longer tenable. 2) If augmented input from vagal pulmonary afferents (which may be stimulated by pulmonary edema, changes in lung compliance or local humoral mediators) are, in part, responsible for the depression in baroreflex sensitivity known to occur in HF. This experiment will be carried out in chronically lung denervated dogs with and without HF. 3) The extent to which cardiac mechano- and chemoreflexes are altered in HF. Based on preliminary data we hypothesize that reflexes emanating from unmyelinated C-fiber afferents may be enhanced following the induction of chronic HF. 4) If the sensitivity of cardiac and pulmonary afferents are altered in HF. Recordings will be made from vagal and sympathetic fibers from the lungs and the heart from sham and HF dogs. We will determine if afferents from the lungs of dogs with HF respond normally to various mechanical stimuli such as pulmonary hyperinflation and lung congestion. Studies will be carried out before and after reduction of pulmonary edema. The response of these endings to chemical stimuli also will be examined in HF dogs. We will concentrate in these studies on substances known to stimulate C-fiber afferents, such as prostaglandins and bradykinin. Similar experiments will be carried out for cardiac afferents. Mechanical stimuli will include ascending aortic and vena caval occlusions. Chemical stimuli will include intracoronary and topical application of prostaglandins, arachidonic acid and bradykinin.